Lung Cancer Cell Lines Inhibit Leukotriene B₄ Production by Human Polymorphonuclear Leukocytes at the Level of Phospholipase A₂

We studied cellular interactions between human polymorphonuclear leukocytes (PMN) and lung cancer cell lines by investigating the influence of cancer cells on the production of leukotriene B₄ (LTB₄) and superoxide anion (O₂^-) by stimulated PMN. Of the nine cancer cell lines established from human lung cancers that we examined, H23 cells showed the highest LTA₄ hydrolase activity. When PMN were stimulated by the calcium ionophore A23187 in the presence of H23 cells, the production of LTB₄, 5(S)-hydroxyeicosatetraenoic acid (5-HETE), and 12(S)-hydroxyeicosatetraenoic acid (12-HETE) decreased in a dose-dependent manner. On the contrary, H23 did not inhibit O₂ production by PMN. Two other cell lines (N417 and Q9) caused similar inhibition of LTB₄ production by PMN. These three cancer cell lines alone did not generate any metabolites of the arachidonic acid (AA) lipoxygenase pathway or any O₂ upon stimulation with A23187 alone. The addition of AA dose-dependently reversed the H23-induced inhibition of LTB₄, 5-HETE, and 12-HETE production by PMN, suggesting inhibition at the phospholipase A₂ (PLA₂) level. Furthermore, addition of the cancer cell line Q9 inhibited ¹⁴C release from [¹⁴C]AA prelabeled PMN in a cell number-dependent manner in the buffer, with and without albumin. The supernatant of H23 cells also inhibited the production of LTB₄ by PMN stimulated by A23187, as did the addition of H23 lysate or its 10⁴ × g centrifugation supernatant. While neither the 10⁵ × g supernatant (cytosol) nor the pellet (microsome) exhibited inhibitory activity, the combination of the separated cytosol and microsomal fractions restored the inhibitory activity. Furthermore, addition of the 10⁴ × g supernatant of Q9 lysate to partially purified human cytosolic PLA₂ inhibited PLA₂ activity in a dose-dependent manner. Our results indicate that the lung cancer cell lines used in our study inhibit LTB₄ production by human PMN through inhibition of phospholipase A₂ activity, which may contribute to a predisposition to pulmonary infections in patients with lung cancer.